ACR Annual Meeting: Janssen’s Tremfya Nails Primary Endpoints in 24-Week Psoriatic Arthritis Studies

Arthritis

Janssen, a Johnson & Johnson company, and Atul Deodhar of Oregon Health & Science University (OHSU) are presenting new Phase III clinical data of Tremfya (guselkumab) in psoriatic arthritis (PsA) at an oral plenary session and a late-breaking poster session at the American College of Rheumatology and Association of Rheumatology Health Professionals (ACR/ARHP) 2019 Annual Meeting.

Deodhar, professor of Medicine, Division of Arthritis and Rheumatic Diseases and medical director of the Rheumatology Clinic in the School of Medicine at OHSU, spoke with BioSpace ahead of his oral presentation on the DISCOVER-1 trial, which was Sunday, November 10. The data from the DISCOVER-2 trial is being presented on Tuesday, November 12 as an e-poster presentation by Philip Mease, director of Rheumatology Research, Swedish-Providence-St. Joseph Health Systems and clinical professor, University of Washington.

Both DISCOVER 1 and DISCOVER 2 are evaluating Tremfya in adults with active psoriatic arthritis. Tremfya is a human monoclonal antibody against the p19 subunit of interleukin (IL)-23. It has been approved by the U.S. Food and Drug Administration (FDA) and other regulatory agencies for moderate to severe plaque psoriasis. Both trials are randomized, double-blind, multi-center Phase III studies. DISCOVER-1 evaluated 381 patients, including ones previously treated with anti-TNF therapy, and continues through 52 weeks. DISCOVER-2 included 739 biologic-naïve participant and will continue through 100 weeks.

Deodhar says the biggest difference between the two studies is that DISCOVER-2 is also evaluating radiographic improvement. The primary endpoint for DISCOVER-1 was ACR20 at week 24. ACR20 is a composite measurement defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure, visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

There were multiple secondary endpoints, including ACR50/70, resolution of soft tissue inflammation (enthesitis and dactylitis), disease activity (DAS-28 CRP), improvement in physical function (HAQ-DI), skin clearance (IGA), and quality of life (SF-36 PCS and MCS).

Deodhar said, “95% of patients completed the study at 24 weeks. The primary endpoint was very statistically significant. ACR20 response at week 24 was 22.2% for placebo, 52% at the low dose, and 59.4% for the higher dose.”

Out of the numerous secondary endpoints, which were pre-selected, Deodhar noted four in particular: IGA, the HAQ-DI, quality of life, and the AR50/70 figures.

“Number one,” Deodhar said, “is skin, because it’s psoriatic arthritis. The IGA, which stands for investigator global assessment, is ranked from 0 to 4, with zero completely clear skin, 1 minimal, 2 mild, 3 moderate, and 4 severe. It’s just the investigator’s opinion, but the IGA score requires patients have a score of 0 or 1 in order to have a reduction of 2 grades. But it’s the most important secondary skin parameter, and it was quite dramatic. Patients in the high dose had 75% IGA endpoint compared to 57% in the low dose and only 15% in the placebo cohort.”

For the HAQ-IQ score, which measures improvement in physical function, Deodhar told BioSpace, “it was significantly reduced in the high dose by 0.4, by 0.32 in the low dose, and 0.07 in the placebo group. HAQ score is 0 to 3, so 0.3 is clinically significant.”

The quality of life has several different measurements, but Deodhor said the physical component score (PCS) “improved by 6.87 in the high dose, 6.10 in the low dose, and 1.9  in the placebo group. All are statistically significant measures, skin, function and quality of life.”

The other secondary measures also were “quite significant,” he noted.

According to Janssen, the company has submitted regulatory data to the FDA for this indication and expects to submit to the European Medicines Agency (EMA) before the end of the year.

Deodhar also indicated that the safety profile for Tremfya in the DISCOVER-1 trial “was excellent. The serious adverse events were 4% in the placebo group, 1.6% in the active group, which means numerically less serious adverse events. The serious infections were about equal for both the placebo side and the drug side.”

One patient died of a heart attack, but since the study is blinded, Deodhar does not know if there was any connection to the drug or which group that patient was in.

“The bottom line,” Deodhar said, “is this looks very promising. This is a completely different and new mode of action. There are other drugs with the same mode of action, but they haven’t completed their Phase II trials. These are the first to complete two major studies in Phase III and it looks very promising and safe.”

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